Objective To investigate the changes in the expression of inflammatory cytokines in serum and aorta of rats with chronic renal failure.Methods Animal model of chronic renal failure was established by single nephrectomy and partial ligation of the contralateral renal artery.The rats were randomly divided into three groups(10 each):normal control group(Con),chronic renal failure group(CRF),rats with chronic renal failure and treated with proteasome inhibitor MG-132 group(CRF+M).The protein expression of TNF? was detected by immunohistochemistry and image analysis,the levels of TNF? and IL-1? of peripheral blood mononuclear cells(PBMC) in blood plasma and culture supernatant were detected by ELISA.Results The protein expression of TNF? 4 and 6 months after operation significantly increased in aorta of CRF group compared with that in CON group(10.7?1.3 vs 4.3?1.7,12.6?2.2 vs 4.3?1.1,P

Ankle brachial index(ABI),as a non-invasive and simple detection method,can be used to accurately assess and diagnose the severities and prognosis of the diabetic lower extremity arterial disease,cardiovascular and cerebral vascular diseases.

BACKGROUND:Studies have shown that the reason of the slower liver regeneration in individuals of cirrhotic liver after partial hepatectomy compared with healthy liver may be related to the delayed synthesis and secretion of hepatocyte growth factor during liver regeneration, but the cause of this phenomenon is not clear. The hepatocyte growth factor activator inhibitor found in recent years can indirectly inhibit the activation of hepatocyte growth factor, but there is little research to explore the expression of hepatocyte growth factor activator inhibitor in the regeneration process after partial hepatectomy in cirrhotic liver and its relationship with the liver regeneration. OBJECTIVE:To investigate the expression of hepatocyte growth factor activator inhibitors (HAI-1, HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy through establishing the cirrhotic rat model, and to explore the biological effects of HAI-1, HAI-2 in cirrhotic liver during the liver regeneration after partial hepatectomy. METHODS:We used 40%CCl4 subcutaneous injection to establish the cirrhotic rat model, then we performed 70%liver resection for the experimental group. The rats in the control group only received ordinary water feeding and 70%liver resection. Rats in each group were randomly sacrificed before surgery and at 3 hours, 6 hours, 12 hours, 24 hours and 48 hours after surgery, and samples were col ected. We used RT-PCR technology to detect the expression of HAI-1 mRNA, HAI-2 mRNA in splenic tissue. RESULTS AND CONCLUSION:The expression levels of HAI-1 mRNA of two groups after partial hepatectomy were increased firstly and then decreased. The expression of HAI-1 mRNA in cirrhotic rats was sustained higher than that of the control group (P<0.05), there was no significant difference between the two groups of the expression of HAI-2 mRNA (P>0.05). The expression of HAI-1 mRNA in liver cirrhosis rats after resection was consistently higher than that in healthy rats, which may lead to the insufficient synthesis and secretion of hepatocyte growth factor activator in cirrhotic rats, then hepatocyte growth factor precursor may not be activated enough, eventual y leading to slow liver regeneration. HAI-2 may not be involved in the wound repair process of liver.

Objective To study the promoting effects and mechanisms of interleukin-22 on liver regeneration in GCl4-induced liver fibrosis mice after partial hepatectomy.Methods One hundred and fortyfour C57/BL6 mice were randomly divided into four groups:PHX group,CCl4 group,CCl4 + PHX group,and CCl4 + IL22 + PHX group.The blood samples were taken to measure serum ALT and AST levels.ALT /AST was calculated to observe the liver injury at 3 h,6 h,12 h,24 h,48 h and 72 h after hepatectomy.The liver tissue specimens were collected at each time point after hepatectomy.We measured the hepatic lobe to calculate the liver weight ratio and conducted pathological examinations to observe the degree of fibrosis and pathological changes at each time point.The positive expression of proliferating cell nuclear antigen (PCNA) in liver tissue was tested by immunohistochemistry.The level of CyclinD1 and STAT3 (Signal transducer and activator of transcription 3) signaling pathway was detected by Western blot.Results (1) Compared with CCl4 + PHX group,the ALT/AST ratio of CCl4 + IL22 + PHX group was significantly higher at 24 h,48 h and 72 h,and the level of ALB of CCl4 + IL22 + PHX group was obviously increased at 48 h and 72 h (P ＜ 0.05).(2) The liver regeneration was significantly increased in CCl4 + IL22 + PHX group.Compared with CCl4 + PHX group (2.08 ± 0.16,2.77 ± 0.07,2.97 ± 0.14),the liver weight ratio of CCl4 + IL22 + PHX group(2.34 ± 0.07,3.23 ± 0.09,3.55 ± 0.09) dramatically increased at 24 h,48 h and 72 h.Moreover,the pathological sections displayed that the disease was alleviated (P ＜ 0.05).(3) Immunohistochemical assay and western blot revealed that compared with other three groups,the level of PCNA,STAT3 and Cyclin D1 was significantly lower in the CCl4 + PHX group.However,the level of PCNA,STAT3 and Cyclin D1 apparently increased in CCl4 + IL22 + PHX group at 24 h,48 h and 72 h (P ＜ 0.05).Conclusion Interleukin-22 may significantly promote liver regeneration and reduce liver pathological injury in liver fibrosis mice induced by administration of CCl4 after hepatectomy,which plays a positive role in the recovery of liver function.

Objective To explore a reliable method of 70% hepatectomy model in liver fibrosis mice. Methods Sixty-six C57BL6 mice were randomly devided into control group (n=6), the traditional group (n=30, ligation and removal liver lobe) and improved group (n=30, removal of liver lobe after blocking blood flow). Those 60 mice were induced liver fibrosis firstly, then randomly divided into six mice in each group, and were sacrificed at preoperative, 12, 24, 48 and 72 hours after liver resection. Liver tissues and blood samples were collected. The survival rate and incidence of complications were recorded and compared between two groups. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to observe the liver injury after 70%hepatectomy. The ratio of liver weight to body weight and the expression of proliferating cell nuclear antigen (PCNA) were also measured to observe the difference of liver regeneration between the two groups. Results (1) Compared to the pathological control group, liver fibrosis model was established successfully in both traditional group and improved group, which can be used in 70%hepatectomy. So the follow-up experiment can be undertook timely. (2) Compared to traditional group, the survival rate was improved significantly in improved group (96.67%vs. 73.33%), and the incidence of complications was significantly lower (P<0.05). (3) The ALT and AST levels were higher 12 h and 24 h after operation in traditional group than those of improved group (P<0.05), while ALT and AST levels were increased first 12 h after operation and then decreased in both groups (P<0.05). (4) The liver/body weight ratio showed a decreasing trend 12 h after hepatectomy in two groups. The expression of PCNA increased at the beginning of postoperative, and reached its peak at 48 h (P<0.05). However, there was no significant difference at each time point between the two groups. Conclusion By blocking blood flow to establish 70% hepatectomy model in liver fibrosis mice, we can significantly improve the success rate of the model, and reduce the incidence of complications.

Objective To investigate the differential expression of hepatocyte growth factor activator (HGFA) and its inhibitors (HAI-1,HAI-2) during cirrhotic and normal liver regeneration after partial hepatectomy,and to explore the causes of the delayed liver regeneration after partial hepatectomy in cirrhotic rat model.Methods We used 40％ CCl4 subcutaneous injection to establish the cirrhotic rat model,and then performed 70％ liver resection for the experimental group together with no operation for the healthy rats as control group.Rats in each group after 3 hours,6 hours,12 hours,24 hours and 48 hours were randomly sacrificed and specimens were collected.The serum HGFA was detected by enzyme-linked immunosorbent assay (ELISA),and we used RT-PCR to detect the mRNA expressions of HAI-1 and HAI-2 in splenic tissue.Results The serum HGFA level in cirrhotic rats at each time point was all significantly lower than that in the control group (P ＜0.05).The expression of HAI-1 mRNA in cirrhotic rats was sustained at a higher level than that in the control group (P ＜ 0.05),but there was no significant difference on the HAI-2 mRNA expression between the two groups (P ＞ 0.05).Conclusions The synthesis of HGFA during the liver regeneration after partial hepatectomy in cirrhosis rats is lower compared with healthy rats,which may lead to the insufficient activation of HGF precursor,eventually causing the slow liver regeneration.HAI-2 may not be involved in the healing process of liver.

Aim To illustrate the actions and molecular mechanisms of interventions taken to convert the metabolism pathways of cellular apoptosis caused by hypoxia and hypoxia-reperfusion in hypertrophic cardiomyocytes.Methods Angiotensin Ⅱ(0.1 ?mol?L-1)was applied to induce the hypertrophy of mice cardiomyocytes.The cardiomyocytes received the treatment of hypoxia-reperfusion in a tri-gas incubator to simulate the conditions of hypoxia-reperfusion.Before hypoxia/reperfusion,no drug intervention and pre-treatments of DCA(1 mmol?L-1),TMZ(5 ?mol?L-1),LC(50 ?mol?L-1)and AA(10 ?mol?L-1)were given respectively.The glucose and fatty acid oxidative metabolism rates were measured with radioactive counting methods.RT-PCR and Western blot methods were employed respectively to measure the mRNA and protein expression levels of cytochrome C and apoptosis inducers.The spectrophotometry method was used to measure the activity of Caspase-3 and Hoechst 33258 staining to quantify the percentage of cellular apoptosis.Results At post-hypoxia 12 h and post-reperfusion 4 h,the glucose oxidative metabolism rates in hypertrophic cardiomyocytes all decreased while the fatty acid oxidative metabolism rates increased.DCA,TMZ and LC all could inhibit both the reduction of glucose oxidative metabolism after hypoxia-reperfusion and the elevation of fatty acid oxidative metabolism after hypoxia-reperfusion.AA drove the reduction of glucose oxidative metabolism rate even lower and the fatty acid oxidative metabolism rate even higher in hypertrophic cardiomyocytes after ischemia/reperfusion.At the same time,DCA,TMZ and LC could inhibit the expression levels of mitochondrial cytochrome C and AIF mRNA and proteins,the nuclear translocation of cytochrome c and AIF proteins and the activity of caspase-3.And with the opposing actions to AA,DCA,TMZ and LC could inhibit the apoptotic rate of hypertrophic cardiomyocytes after hypoxia-reperfusion.And AA had the opposite effect.Conclusion Intervening in the metabolism pathway of hypertrophic cardiomyocytes was an effective way to prevent and control their programmed death through inhibiting the expression of mitochondrial apoptotic proteins.

Objective:To investigate the effects of Yukuiqing (YKQ) on the expression of connective tissue growth factor (CTGF) in cultured human renal mesangial cells (HRMC) incubated with AGEs. Methods:The HRMCs were incubated with AGEs (200 ?g/mL) and 1.25% YKQ which was prepared by Chinese herbal medicine serum pharmacological approach for 0,8,16,24,48 and 72h or different concentrations (0.313%,0.625% and 1.25%) of YKQ for 48h,respectively,which were incubated with DMEM and rat serum (RS) as the control. CTGF mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western Blotting respectively. Results:In Yukuiqing group,the expression of CTGF mRNA and protein decreased significantly compared with control groups (P

Objective To investigate the correlation of ankle-brachial index(ABI),pulsatility index(PI),resistent index(RI)and vibration perception thresholds(VPT)in type 2 diabetic patients(T2DM).Methods A total of 664 type 2 diabetic patients with 1 328 legs(362 men and 302 women)were divided into three groups based on the ABI test: group A(ABI

Objective To investigate the activation of NF-κB and regulation by ubiquitin (Ub)-proteasome pathway in the aorta of rats with chronic renal failure(CRF).Methods The CRF rat model was established by right nephreetomy and left branch renal artery ligation.The CRF rats were were randomly divided into simple CRF group(n=20)and CRF+M used as control group(CON).The NF-κB and the Ub mRNA expression were detected by RT-PCR,and its protein expression was analyzed by immunohistochemistry method.The activity of NF-κBwas mesured by EMSA method.The concentration of IL-1 and TNF-α was detected by ELISA.Results Compared with the CON group,the concentration of serum IL-1 and TNF-α was increased significantly in CRF group [IL-1:(9.02±1.29) vs (2.74±0.96)mg/L,P＜0.01;TNF-α:(50.02±9.52) vs (14.04±1.29)mg/L,P＜0.01]at month 4 after operation.The mRNA expression of NF-κB and Ub in the aorta of CRF group was 1.38 and 1.29 times as that of CON group(P＜0.01).and the protein expression of NF-κB and Ub was 3.75 and 20.5 times as that of CON group(P＜0.01).Compared with the CON group,the activity of NF-κB in the aorta of rats of CRF group was elevated markedly at month 4 after operation(P＜0.01).All the indices were further increased at month 6 after operation.Compared with CRF group,the concentrations of serum IL-1and TNF-α were decreased significantly in CRF+M group[IL-1:(2.94±0.33)mg/L,P＜0.01;TNF-α:(12.80±2.12)mg/L,P＜0.01].The mRNA and protein expression of NF-κB and Ub were also decreased markedly(P＜0.01),and the activity of NF-κB was decreased significantly at month 4 to 6 after operation(P＜0.01).But the amount of ubiquitnative protein was increased significantly in the aorta of CRF+M group as compared to CRF group(P＜0.01). Conclusion The inflammatory signal pathway of ubquitin-proteasome-NF-κB pathway was activated in the aorta of CRF rats,and the proteasome was probablely an important pharmacological intervention target to regulate the activation of NF-κB.